Active substances used in the pharmaceutical industry frequently have an objectionable taste. This presents difficulties in the development of formulations because objectionable taste can lead to poor patient compliance. This problem is particularly severe in liquid, chewable and fast dissolving dosage forms. There are two main techniques known in the art for masking this taste. The first is to add flavors to hide the objectionable taste. The second is to limit the dissolution of the active substance in the saliva.
There are currently no in vitro test methods designed for assessing the taste masking properties of taste-masked formulations. There are a multiplicity of tests available for in vitro testing of dissolution of formulations intended for gastro-intestinal (GI) dissolution (US Pharmacoapeia 24), but none of them are suitable for buccal systems. For the purposes of this discussion such methods will be referred to as GI dissolution methods. Buccal dissolution is characterized by some unique requirements. Firstly, for taste masking, incomplete buccal dissolution is a highly desirable property, whereas a primary aim of all GI dissolution methods is complete dissolution. Secondly, buccal residence times are very short, of the order of several minutes, based on saliva secretion rates. GI residence times are of the order of hours. Thirdly, undissolved components, for example small particles, are removed from the mouth by swallowing so that their residence time is of the order of 5-60 seconds. No current GI dissolution tests make allowance for removal of undissolved components from the test chamber.
Since dissolved compounds can impart a bad taste, there is a need in the art for an in vitro test method that can characterize the dissolution of compounds in the buccal cavity under conditions that are physiologically relevant.
Applicants have invented a test method and apparatus that satisfies this need.
The following terms have the following meanings herein:
The term “release medium” as used herein, means the liquid medium into which the substance is being released. Examples of release media can be simulated saliva, water, and various buffer solutions.
The term ‘residence time’ as used herein, is a well known engineering concept applied to continuous flow systems, and is calculated by mathematically dividing the volume of liquid in a vessel by the flow rate into an out of the vessel such that the volume of liquid remains constant. For example, a flow rate of 5 ml/min into and out of a vessel containing 10 ml of liquid has a residence time of 2 minutes.
The term ‘resinate’ as used herein, means the product derived from forming a complex between an ion exchange resins and an ionizable organic compound.